In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis

Rafael L. Ufret-Vincenty, Laura Quigley, Nancy Tresser, Seong Hee Pak, Ameer Gado, Stefan Hausmann, Kai W. Wucherpfennig, Stefan Brocke

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

A peptide derived from the human papillomavirus L2 protein is recognized by a myelin basic protein (MBP)-specific T cell clone from a multiple sclerosis patient and by MBP-specific autoantibodies purified from multiple sclerosis brain tissue. We now show in mice that low doses of this papillomavirus peptide were optimal in selecting a subpopulation of papillomavirus peptide-specific T cells that cross-reacted with MBP(87-99) and with an unrelated viral peptide derived from the BSLF1 protein of Epstein-Barr virus (EBV). These low dose viral peptide-specific T cell lines were highly encephalitogenic. Splenocytes from mice transferred with viral peptide-specific T cells showed a vigorous response to both the papillomavirus and MBP peptides, indicating that viral antigen-specific T cells survived for a prolonged time in vivo. The EBV peptide, unable to prime and select an autoreactive T cell population, could still activate the low dose papillomavirus peptide-specific cells and induce central nervous system (CNS) autoimmunity. Cytokine profiles of papillomavirus peptide-specific encephalitogenic T cells and histopathology of CNS lesions resembled those induced by MBP. These results demonstrate conserved aspects in the recognition of the self-antigen and a cross-reactive viral peptide by human and murine MBP-specific T cell receptors. We demonstrate that a viral antigen, depending on its nature, dose, and number of exposures, may select autoantigen-specific T cells that survive in vivo and can trigger autoimmune disease after adoptive transfer.

Original languageEnglish (US)
Pages (from-to)1725-1738
Number of pages14
JournalJournal of Experimental Medicine
Volume188
Issue number9
DOIs
StatePublished - Nov 2 1998

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Autoimmune Experimental Encephalomyelitis
Viral Antigens
T-Lymphocytes
Peptides
Myelin Basic Protein
Peptide T
Autoantigens
Human Herpesvirus 4
Multiple Sclerosis
Central Nervous System
Adoptive Transfer
T-Cell Antigen Receptor
Autoimmunity
Autoantibodies
Autoimmune Diseases
Proteins
Clone Cells
Cytokines
Cell Line
Brain

Keywords

  • Antigenic peptide
  • Autoimmunity
  • Cross-reactivity
  • Experimental autoimmune encephalomyelitis
  • Molecular mimicry

ASJC Scopus subject areas

  • Immunology

Cite this

In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. / Ufret-Vincenty, Rafael L.; Quigley, Laura; Tresser, Nancy; Pak, Seong Hee; Gado, Ameer; Hausmann, Stefan; Wucherpfennig, Kai W.; Brocke, Stefan.

In: Journal of Experimental Medicine, Vol. 188, No. 9, 02.11.1998, p. 1725-1738.

Research output: Contribution to journalArticle

Ufret-Vincenty, RL, Quigley, L, Tresser, N, Pak, SH, Gado, A, Hausmann, S, Wucherpfennig, KW & Brocke, S 1998, 'In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis', Journal of Experimental Medicine, vol. 188, no. 9, pp. 1725-1738. https://doi.org/10.1084/jem.188.9.1725
Ufret-Vincenty, Rafael L. ; Quigley, Laura ; Tresser, Nancy ; Pak, Seong Hee ; Gado, Ameer ; Hausmann, Stefan ; Wucherpfennig, Kai W. ; Brocke, Stefan. / In vivo survival of viral antigen-specific T cells that induce experimental autoimmune encephalomyelitis. In: Journal of Experimental Medicine. 1998 ; Vol. 188, No. 9. pp. 1725-1738.
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